Objective: The mechanism of sex difference in cardiovascular disease has not yet been elucidated, and this proposal would investigate basic arterial wall processes which could relate to this sex difference. The specific objectives are to study the effects of estrogen, progesterone, testosterone, and contraceptive steroids on collagen and elastin synthesis, degradation, and net accumulation in rat aortas. Systolic blood pressure, vascular wall stiffness, and vascular reactivity will be measured. The hormonal status of the animals will be altered and controlled by deprivation procedures followed by replacement therapy and will be assessed terminally by radioimmunoassay. We would thus propose to test the hypothesis that sex hormones alter arterial wall properties by altering collagen and elastin metabolism in arterial wall. Methods: Rats will be castrated and replacement therapy or oil vehicle control substances administered. Systolic blood pressure will be measured periodically. At the end of the treatment period C14-proline will be administered and rats from each group will be killed in four different successive time periods. Specific activity of hydroxyproline and total accumulation of both collagen and elastin of aorta will be determined. Vessels will be removed for determination of vascular stiffness and reactivity. Chemical methods employed include hydrolysis of proteins, column chromatographic separation of proline and hydroxyproline, colorimetric determination of hydroxyproline, and liquid scintillation detection of radioactivity. Vascular stiffness and reactivity are determined from stress-strain analysis of whole vessel segments using equipment specially built for this purpose.